Anti-inflammatory medicinal agent

FIELD: pharmacy.

SUBSTANCE: invention proposes a medicinal agent for oral administration possessing an anti-inflammatory effect. Medicinal agent is made as a solid dosed formulation for oral administration that comprises meloxicam as an active substance, stearic acid or stearate as a slipping substance, maltodextrin as a binding agent, croscarmellose sodium salt as a disintegrating agent and dextrin as a filling agent taken in the definite ratio of components. Invention provides enhancing the biological availability of agent and improving its consumption properties. Invention can be used in the development of a medicinal agent made as a solid dosed formulation for oral administration possessing an anti-inflammatory effect.

EFFECT: improved and valuable pharmaceutical properties of agent.

10 cl, 11 tbl, 32 ex

 

The present invention relates to medicine, namely to the pharmaceutical industry, and can be used to create medicines made in the form of solid dosage forms for oral administration, which has anti-inflammatory action.

Currently there is a large Arsenal of non-steroidal anti-inflammatory drugs (NSAIDs). Interest in their development is related to the fact that NSAIDs have anti-inflammatory, analgesic and antipyretic effects and bring relief to patients with relevant symptoms (inflammation, pain, fever), which are observed in many diseases.

Substance meloxicam is a highly effective, low-toxicity drug of a new generation of NSAIDs, has minimal gastrointestinal action.

Known tablets Movalis® company Boehringer Ingelheim, containing meloxicam in the amount of 7.5 mg and 15 mg per tablet, and other ingredients are: sodium citrate, lactose, microcrystalline cellulose, polyvidone, silicon dioxide colloidal anhydride, crospovidone, magnesium stearate (reference Vidal drugs of Russia", Attraversare, 2003, strb-594). These tablets include microcrystalline cellulose, which affects the processes of dissolution and raspadaemosti tablets, reduces the bioavailability of the drug.

Known tablet with meloxicam, obtained by direct pressing (WO 99/49867, 27.03.1998, Boehringer Ingelheim Pharma). The composition of this tablet also includes microcrystalline cellulose, which is slowing down the processes of dissolution and raspadaemosti tablets, reduces the bioavailability of the drug.

Closest to the claimed means the technical essence and the achieved result is a well-known tool that is described in the international application WO 02/085331 from 21.04.2001, the applicant Boehringer Ingelheim International (Germany).

Known means made in the form of tablets which contains meloxicam 1 mg - 20 mg, or its pharmaceutically acceptable salt to a tablet weight of 20 mg to 800 mg, the binder is a starch, in particular modified, or several varieties, moving, in particular silicon dioxide, and a filler, in particular dextrose in an amount of from 40 to 80%.

However, contained in the composition of the tablets starch reduces its bioavailability, and the totality of its components is not possible to obtain a smooth surface, which impairs the consumer properties of the tablets.

The problem solved by the invention is the creation of anti-inflammatory drugs, made in solid dosage form for oral administration, containing as active substance meloxicam with high bioavailability and improved and consumer properties, expanding the Arsenal of anti-inflammatory action.

The technical result from the use of the invention is to improve the bio availability of anti-inflammatory drugs in solid dosage form for oral administration, contains meloxicam as the active substance, and in improving its consumer properties.

This result is achieved by the fact that anti-inflammatory drug, is made in the form of solid dosage forms for oral administration containing as active substance meloxicam, moving, a binder and a filler according to the invention as a binder it contains maltodextrin, as moving it contains a salt of stearic acid or stearic acid, as a filler it contains dextrin and further comprises a disintegrator, in particular the sodium salt croscarmellose, with the following content, wt.%:

Meloxicam - 4,0-25,0

Disintegrator - sodium salt croscarmellose - 0,5-7,0

Binder is maltodextrin - 5,0-20,0

Moving - salt of stearic acid

or stearic acid - 0,3-1,0

Filler - dextrin - 100

Preferably, as salts of stearic acid using magnesium or to llevue salt.

It is preferable that the proposed tool is made in the form of tablets, or microtablets, or pellets, or granules.

It is preferable that the mass of the tablet is 0.1 g and 0.2 g

It is preferable that the size of microtablets is 1.5-3 mm.

It is preferable that the size of the pellets or granules is 0.25 to 3.0 mm

It is preferable that the proposed tool, made in the form of tablets or microtablets, or pellets, or granules coated polymer based.

Preferably, the membrane mass relative to the mass of the nucleus is, wt.%: for tablets 5-13, for microtablets 5-13, for pellets 15-25, granules 25-40.

It is preferable that a number of microtablets, or pellets, or granules may be placed in a pharmaceutically acceptable capsule for oral administration.

Preferably, the capsule is filled with microtablets, or pellets, or granules in such a quantity that the concentration of active ingredient equivalent to therapeutic dose.

The proposed ratio of these ingredients is found experimentally and is optimal.

That the proposed remedy as a binder contains maltodextrin as a filler - dextrin, as the moving - salt of stearic acid or stearic acid, and additionally who will win the disintegrator - sodium salt croscarmellose, allows to obtain the drug, which has high biological availability. The high bioavailability of the proposed funds due to the synergistic effect, which is achieved due to the simultaneous introduction of the proposed composition of these components at the given value.

In addition, the tablet is made of the proposed facilities, has an important consumer property - smooth surface.

Floor offer a means of shell-based polymer is technologically feasible and allows you to mask an unpleasant taste.

The implementation of the proposed funds in the form of microtablets, granules or pellets and placing them in a pharmaceutically acceptable capsule allows you to more evenly distribute the active substance in the gastrointestinal tract.

The content of active substance in the proposed tool is less than 4.0 wt.% leads to a decrease in therapeutic effect, and the increase in the content of the active substance more to 25.0 wt.% leads to side effects.

The method of obtaining the proposed funds in the form of tablets or microtablets.

The estimated number of meloxicam is mixed with part of the cage - sodium salt croscarmellose, the binder is maltodextrin and filler - dextrin. Recip is nnow the mixture is moistened with water. From a mixture of receive granules, which are dried at a temperature of 55°With, calibrate, optivault mixture moving calcium stearate and the remaining part of the cage and tabletirujut. At the core of tablets or microtablets may be caused to the shell component 5-13 wt.% from the mass of the nucleus.

The method of obtaining the proposed funds in the form of pellets or granules.

The estimated number of all components are mixed, the resulting mixture is moistened. The resulting mixture is get pellets or granules. At the core of the pellets or granules may be applied to the shell component of 15-25 wt.% and 25-40 wt.% by weight of the core pellets or granules, respectively.

Received microtablets, or pellets, or granules can be placed in a pharmaceutically acceptable capsule, for example made of gelatin, in such a quantity that the concentration of active ingredients equivalent to therapeutic dose.

In the described ways of obtaining the proposed tool uses meloxicam that meets the requirements of BP; the sodium salt of croscarmellose, meets the requirements of BP or Eur.Ph, maltodextrin, meets the requirements of BP or Eur.Ph, calcium stearate, meets the requirements of THE 6-09-4233-76, dextrin, meets the requirements of BP or Eur.Ph.

The following are specific examples of the manufacture of the proposed funds in the form of tablet is or microtablets.

Example 1.

Take 25,0 kg of meloxicam, mixed with 4.2 kg of sodium salt of croscarmellose, 20,0 kg maltodextrin and dextrin to 100 kg. Mass of hydrate water and granularit. The obtained granules are dried at a temperature of 55°With, calibrate, optivault mixture consisting of 1.0 kg of calcium stearate and 2.8 kg sodium salt croscarmellose, and tabletirujut. Tablet mass has the following composition, wt.%:

Meloxicam - 25,0

Sodium salt croscarmellose - 7,0

Maltodextrin - 20,0

Calcium stearate - 1,0

Dextrin and 47.0

Example 2.

Take 25,0 kg of meloxicam, mixed with 0.3 kg of sodium salt of croscarmellose, 5,0 kg maltodextrin and dextrin to 100 kg. Mass of hydrate water and granularit. The obtained granules are dried at a temperature of 55°With, calibrate, optivault mixture consisting of 0.3 kg of calcium stearate and 0.2 kg of sodium salt of croscarmellose, and tabletirujut. Tablet mass has the following composition, wt.%:

Meloxicam - 25,0

Sodium salt croscarmellose - 0,5

Maltodextrin - 5,0

Calcium stearate and 0.3

Dextrin - 69,2

Example 3.

Is carried out as example 1, only take 5,0 kg maltodextrin, 0.3 kg of calcium stearate. Tablet mass has the following composition, wt.%:

Meloxicam - 25,0

Sodium salt croscarmellose - 7,0

Maltodextrin - 5,0

Calcium stearate - 1,0

Dextrin - 62,7

Example 4.

p> Is carried out as example 1, only take 0.3 kg of calcium stearate. Tablet mass has the following composition, wt.%:

Meloxicam - 25,0

Sodium salt croscarmellose - 7,0

Maltodextrin - 20,0

Calcium stearate and 0.3

Dextrin - 47,7

Example 5.

Is carried out as example 1, only take 4,0 kg of meloxicam, 20,0 kg maltodextrin, 1.0 kg of calcium stearate. Tablet mass has the following composition, wt.%:

Meloxicam - 4,0

Sodium salt croscarmellose - 7,0

Maltodextrin - 20,0

Calcium stearate - 1,0

Dextrin - 68,0

Example 6.

As example 2, only take 4,0 kg of meloxicam, 20,0 kg maltodextrin, 1.0 kg of calcium stearate. Tablet mass has the following composition, wt.%:

Meloxicam - 4,0

Sodium salt croscarmellose - 0,5

Maltodextrin - 20,0

Calcium stearate - 1,0

Dextrin is 74.5

Example 7.

As example 2, only take 4,0 kg of meloxicam, 1.0 kg of calcium stearate. Tablet mass has the following composition, wt.%:

Meloxicam - 4,0

Sodium salt croscarmellose - 0,5

Maltodextrin - 5,0

Calcium stearate - 1,0

Dextrin - 89,5

Example 8.

Carried out as example 2, only take 1.0 kg of calcium stearate. Tablet mass has the following composition, wt.%:

Meloxicam - 25,0

Sodium salt croscarmellose - 0,5

Maltodextrin - 5,0

Alicia stearate - 1,0

Dextrin and 68.5

Example 9.

Take 4,0 kg of meloxicam, mixed with 4.2 kg of sodium salt of croscarmellose, 20,0 kg maltodextrin and dextrin to 100 kg. Mass of hydrate water and granularit. The obtained granules are dried at a temperature of 55°With, calibrate, optivault mixture consisting of 0.3 kg of calcium stearate and 2.8 kg sodium salt croscarmellose, and tabletirujut. Tablet mass has the following composition, wt.%:

Meloxicam - 4,0

Sodium salt croscarmellose - 7,0

Maltodextrin - 20,0

Calcium stearate and 0.3

Dextrin - 68,7

Received the tablet is covered with a shell-based polymer, which is 13 wt.% by weight of the tablet.

Example 10.

Carried out as example 1, only take 4,0 kg of meloxicam, 5,0 kg maltodextrin, 0.3 kg of stearic acid. Tablet mass has the following composition, wt.%:

Meloxicam - 4,0

Sodium salt croscarmellose - 7,0

Maltodextrin - 5,0

Stearic acid - 0,3

Dextrin - 83,7

Example 11.

Carried out as example 2, only take 4,0 kg of meloxicam, 20,0 kg maltodextrin. Tablet mass has the following composition, wt.%:

Meloxicam - 4,0

Sodium salt croscarmellose - 0,5

Maltodextrin - 20,0

Calcium stearate and 0.3

Dextrin - 75,2

Example 12.

Is carried out as example 1, only take 5,0 kg maltodextrin. Tablet weight and eat the following composition, wt.%:

Meloxicam - 25,0

Sodium salt croscarmellose - 7,0

Maltodextrin - 5,0

Calcium stearate - 1,0

Dextrin - 62,0

Received the tablet is covered with a shell-based polymer, which is 5 wt.% by weight of the tablet.

Example 13.

Carried out as example 2, only take 20,0 kg maltodextrin, 1.0 kg of calcium stearate. Tablet mass has the following composition, wt.%:

Meloxicam - 25,0

Sodium salt croscarmellose - 0,5

Maltodextrin - 20,0

Calcium stearate - 1,0

Dextrin - 53,5

Example 14.

Carried out as example 2, only take 4,0 kg of meloxicam, 0.3 kg of magnesium stearate. Tablet mass has the following composition, wt.%:

Meloxicam - 4,0

Sodium salt croscarmellose - 0,5

Maltodextrin - 5,0

Magnesium stearate - 0,3

Dextrin - 90,2

Example 15.

Carried out as example 2, only take 20,0 kg maltodextrin, 0.3 kg of magnesium stearate. Tablet mass has the following composition, wt.%:

Meloxicam - 25,0

Sodium salt croscarmellose - 0,5

Maltodextrin - 20,0

Magnesium stearate - 0,3

Dextrin - 54,2

Example 16.

Carried out as example 1, only take 4,0 kg of meloxicam, 5,0 kg maltodextrin. Tablet mass has the following composition, wt.%:

Meloxicam - 4,0

Sodium salt croscarmellose - 7,0

Maltodextrin - 5,0

Calcium stearate - 1,0

D is xtren - 83,0

The following are specific examples of the manufacture of the proposed funds in the form of pellets or granules.

Example 17.

Take 25,0 kg of meloxicam, mixed with 7.0 kg of the sodium salt of croscarmellose, 20,0 kg maltodextrin, 1.0 kg of calcium stearate, dextrin up to 100 kg and moisturize. The resulting mass is get pellets or granules. The resulting mass has the following composition, wt.%:

Meloxicam - 25,0

Sodium salt croscarmellose - 7,0

Maltodextrin - 20,0

Calcium stearate - 1,0

Dextrin and 47.0

Example 18.

Take 25,0 kg of meloxicam, mixed with 0.5 kg of sodium salt of croscarmellose, 5,0 kg maltodextrin, 0.3 kg of calcium stearate, mix and moisturize. The resulting mass is get pellets or granules. The resulting mass has the following composition, wt.%:

Meloxicam - 25,0

Sodium salt croscarmellose - 0,5

Maltodextrin - 5,0

Calcium stearate and 0.3

Dextrin - 69,2

Example 19.

As example 17, only take 5,0 kg maltodextrin and 0.3 kg of calcium stearate. The resulting mass has the following composition, wt.%:

Meloxicam - 25,0

Sodium salt croscarmellose - 7,0

Maltodextrin - 5,0

Calcium stearate - 1,0

Dextrin - 62,7

Example 20.

As example 17, only take 0.3 kg of calcium stearate. The resulting mass has the following composition, wt.%:

Meloxicam - 25,0

Three-the first salt croscarmellose - 7,0

Maltodextrin - 20,0

Calcium stearate and 0.3

Dextrin - 47,7

Example 21.

As example 17, only take 4,0 kg of meloxicam, 20,0 kg maltodextrin, 1.0 kg of calcium stearate. The resulting mass has the following composition, wt.%:

Meloxicam - 4,0

Sodium salt croscarmellose - 7,0

Maltodextrin - 20,0

Calcium stearate - 1,0

Dextrin - 68,0

Example 22.

As example 18, only take 4,0 kg of meloxicam, 20,0 kg maltodextrin, 1.0 kg of calcium stearate. The resulting mass has the following composition, wt.%:

Meloxicam - 4,0

Sodium salt croscarmellose - 0,5

Maltodextrin - 20,0

Calcium stearate - 1,0

Dextrin is 74.5

Example 23.

As example 18, only take 4,0 kg of meloxicam, 1.0 kg of calcium stearate. The resulting mass has the following composition, wt.%:

Meloxicam - 4,0

Sodium salt croscarmellose - 0,5

Maltodextrin - 5,0

Calcium stearate - 1,0

Dextrin - 89,5

Example 24.

Carried out as example 18, only take 1.0 kg of calcium stearate. The resulting mass has the following composition, wt.%:

Meloxicam - 25,0

Sodium salt croscarmellose - 0,5

Maltodextrin - 5,0

Calcium stearate - 1,0

Dextrin and 68.5

Example 25.

Carried out as example 17, only take 4,0 kg of meloxicam, mixed with 4.2 kg of sodium salt of croscarmellose, 20,0 kg mA is Icodextrin. The resulting mass has the following composition, wt.%:

Meloxicam - 4,0

Sodium salt croscarmellose - 7,0

Maltodextrin - 20,0

Calcium stearate and 0.3

Dextrin - 68,7

The obtained granules are covered with a shell-based polymer, which is 25 wt.% from the mass of the nucleus.

Example 26.

Carried out as example 17, only take 4,0 kg of meloxicam, 5,0 kg maltodextrin, 0.3 kg of stearic acid. The resulting mass has the following composition, wt.%:

Meloxicam - 4,0

Sodium salt croscarmellose - 7,0

Maltodextrin - 5,0

Stearic acid - 0,3

Dextrin - 83,7

The obtained granules are covered with a shell-based polymer, which is 40 wt.% by weight of the tablet.

Example 27.

Carried out as example 18, only take 4,0 kg of meloxicam, 20,0 kg maltodextrin. The resulting mass has the following composition, wt.%:

Meloxicam - 4,0

Sodium salt croscarmellose - 0,5

Maltodextrin - 20,0

Calcium stearate and 0.3

Dextrin - 75,2

Example 28.

As example 17, only take 5,0 kg maltodextrin. The resulting mass has the following composition, wt.%:

Meloxicam - 25,0

Sodium salt croscarmellose - 7,0

Maltodextrin - 5,0

Stearic acid - 1,0

Dextrin - 62,0

The obtained pellets are covered with a shell-based polymer, which is 15 wt.% by weight I had RA.

Example 29.

Carried out as example 18, only take 20,0 kg maltodextrin, 1.0 kg of calcium stearate. The resulting mass has the following composition, wt.%:

Meloxicam - 25,0

Sodium salt croscarmellose - 0,5

Maltodextrin - 20,0

Calcium stearate - 1,0

Dextrin - 53,5

Example 30.

Carried out as example 18, only take 4,0 kg of meloxicam, 0.3 kg of magnesium stearate. The resulting mass has the following composition, wt.%:

Meloxicam - 4,0

Sodium salt croscarmellose - 0,5

Maltodextrin - 5,0

Magnesium stearate - 0,3

Dextrin - 90,2

The obtained pellets are covered with a shell-based polymer, which is 25 wt.% from the mass of the nucleus.

Example 31.

Carried out as example 18, only take 20,0 kg maltodextrin, 0.3 kg of magnesium stearate. The resulting mass has the following composition, wt.%:

Meloxicam - 25,0

Sodium salt croscarmellose - 0,5

Maltodextrin - 20,0

Magnesium stearate - 0,3

Dextrin - 54,2

Example 32.

Carried out as example 17, only take 4,0 kg of meloxicam, 5,0 kg maltodextrin. The resulting mass has the following composition, wt.%:

Meloxicam - 4,0

Sodium salt croscarmellose - 7,0

Maltodextrin - 5,0

Calcium stearate - 1,0

Dextrin - 83,0

The determination of meloxicam in the proposed tool is carried out by spectrophotometric method.

Test the Oia microbiological purity of tablets obtained in examples 1-32, conducted in accordance with the requirements of the global Fund XI and Changes No. 3, category 3A. The obtained results are in line with regulatory requirements.

Studies have been conducted to study the influence of physical factors such as temperature and light, on the tools described in examples 1-32.

After research it was found that the best storage conditions: in dry the dark place at a temperature not exceeding 25°C.

To determine the General toxic action and evidence of the effectiveness of the proposed drug were conducted its pre-clinical trials.

These tests were carried out on the basis of JSC "all-Russia scientific center for security biologically active substances", Kupavna, 2005

For testing of the proposed drug was presented in the form of tablets. Component content per tablet is presented in the table.

Table

The composition of the proposed drug per tablet
Meloxicam- 7.5 mg
Sodium salt croscarmellose- 5.0 mg
Maltodextrin10 mg
Calcium stearate- 1.0 mg
Dextrin - 76,5 mg

The amount of pre-clinical trials was determined by the Order of Ministry of health of Russia from 19.06.03 No. 267 "On approval of rules of good laboratory practice in the Russian Federation" and the "guidelines for the study of General toxic effect of pharmacological substances" (in Russian). "Manual on experimental (preclinical) study of new pharmacological substances". M., "Remedium", 2000, p.18-24).

The experiments were carried out on outbred rats of both sexes (rat from Rapolano, St. Petersburg, quality passport No. 15 dated 11.01.2005, weighing 150-160 g, age 13-14 weeks).

Before the Study the animals that meet the criteria for inclusion in the study were divided into groups using the method of randomization. Animals that do not meet the criteria for inclusion in the Study, were excluded from the Study during the quarantine.

During the Study, each animal was examined daily. The inspection consisted of evaluating the overall behavior and General condition of the animals. In the days of injecting drug examination was performed approximately 2 hours after injection.

In the list of registered indicators included the dynamics of body weight, water consumption and feed, blood pressure, heart rate (HR).

To determine indicators of acute toxicity of the proposed tool (pills, pounded the onyx mortar to a powder) was administered to rats of both sexes intragastrically in starch suspensions using atraumatic metal probe in increasing doses on Litchville-Wilcoxon signed. Control animals were injected starch suspension. The data presented in table 1.

Table 1

The toxicity of the proposed means when a rat-males (mg/kg)
Dose, mg/kg23.729.337.547.360.0
The effect Palo animals/total0/62/65/65/66/6

LD50=40.3±3.5 mg/kg

LD16=23.7 mg/kg

LD84=43.5 mg/kg

Mortality of animals occurred at 1-4 day after a single injection of the drug on the background of the decrease of motor activity, tremor, haemorrhagic rash around the nose (in some animals), slovenliness, piloerection, the presence of melena. At the necropsy of dead animals were observed hemorrhagic erosions in the mucosa of the gastric body - on pinkish background mucosa were clearly distinguished multiple dark red foci. The contents of the stomach and intestines was dyed with blood.

Macroscopic changes in the other examined organs were missing.

In surviving animals of significant changes state and behavior were noted. Below are data on the effect of drugs on body weight of surviving animals.

Table 2

The impact of the proposed remedies on the body weight of experimental animals (M±m, g)The observation timeControlThe proposed toolMFMFBackground179.5±4.2180.0±3.7180.0±4.3178.5±4.37 days185.0±5.2186.5±6.1182.0±4.1180.5±5.114 days191.5±5.8191.0±6.3185.0±6.1183.0±5.7

After the experiment, the animals were subjected to attanasio to determine the mass ratios of organs and pathological studies. Data on the mass ratios shown in table 3.

As follows from the table, significant differences of the mass coefficients of organs from animals from different experimental groups were observed.

Table 3

Mass () organs of white rats (mg/100 g body weight, M±m)
MKThe studied group and gender
ControlThe proposed tool
MFMF
Heart4.5±0.34.2±0.34.2±0.34.1±0.3
Lungs with trachea9.8±0.49.6±0.39.6±0.38.9±0.5
The thymus1.10±0.021.13±0.021.13±0.021.12±0.03
Liver54.0±4.060.0±4.052.0±5.057.0±4.0
Spleen4.2±0.44.3±0.44.3±0.44.6±0.4
Kidney7.9±0.67.5±0.57.5±0.58.3±0.5
The adrenal glands0.30±0.020.29±0.020.28±0.030.30±0.03
The brain9.4±0.49.7±0.59.6±0.49.5±0.6

According to the autopsy and microscopic studies of the organs of the differences between the surviving animals and the control is not installed.

The coat was shiny, neat appearance. Foci of alopecia is not what was abudals. Allocation of natural holes were missing. The forelimbs and hind limbs intact. Deformation of the limbs were observed. The teeth were saved. Visible mucous membranes were pale, shiny, smooth.

Upon examination of the thoracic and abdominal cavities irregularities in the position of the internal organs were noted.

The pleura, pericardium and peritoneum were thin, shiny, smooth.

Thymus had a triangular shape, whitish color and moderately firm consistency.

Aortic diameter was uniform throughout. The intima of the aorta was smooth, shiny, whitish color. The size and shape of the heart unchanged.

The muscle of the heart was moderately dense, uniformly brownish color. Heart valves are thin, smooth, shiny. In the cavities of the heart contained a small amount of liquid blood.

Light at the opening of the chest was spadolini. The size and shape unchanged. The surface of the lungs had a uniform pale pink color. The lung tissue was fluffy to the touch. The lumen of the trachea and large bronchi was wide. Mucosa - shiny, pale pink, smooth.

Mucosa of the esophagus was shiny, smooth, pale color. The size and shape of the stomach unchanged. The lumen was filled with food content. The lumen of the duodenum 12 unchanged, mucous intestine b is La shiny, smooth, pale pink. The mucous membrane of the small intestine was also pale pink, shiny, smooth. The mucous membrane of the colon had a slightly grayish hue, was smooth and shiny.

The size and shape of the liver unchanged. The surface of the liver was smooth, uniform dark red color. The liver tissue at the incision was dark red. The liver capsule was thin, transparent. The consistency of the liver was normal density.

The shape of the pancreas without changes. Iron had lobed structure, pale pink color and moderately firm consistency.

The size and shape of the spleen intact. The surface of the spleen had a uniform dark cherry color, was smooth. The consistency of the spleen was moderately dense. In the context of organ stood out greyish small-cell follicles.

The size and shape of the kidney as unchanged. The capsule of the kidney can be easily removed. The surface was smooth, uniformly brownish-grayish color. In the context of organ distinct cortical and brain substance. The consistency of the kidneys was moderately tight.

The adrenal glands have a rounded form, whitish-yellow in color and moderately firm consistency. In the context of clearly stood out dark brown cerebral substance.

The bladder was filled with a transparent, pale urine. The mucous membrane is aciago bubble was smooth, shiny, pale color.

The lining of the brain were thin, transparent. The substance of the brain was slightly potowatami to the touch, the surface of the brain was smooth. In the frontal dimensions of ventricular enlargement were observed.

Thus, the obtained experimental data show that a single intragastric administration of the proposed means to rats of both sexes does not cause changes in behavior and General condition of the surviving animals, the mass ratios of the bodies relative to control animals, macroscopic changes in the brain, internal organs and endocrine laboratory animals, and is not accompanied by changes in the mucous membrane of the esophagus, stomach and intestines (the introduction).

Given the sensitivity of rodents and data obtained in the acute experiment, studies were conducted on rats with daily intragastric administration of drugs within 14 days at doses exceeding the maximum daily at 10 and 50 times (in active top). Conditions of the introduction corresponded described in the "Acute toxicity". Animals were identified integral indicators of the status and behavior, heart rate and blood pressure, basic biochemical, morphological composition of peripheral blood, the mass ratios of the bodies and their macro - and microscopy. During the observation period mortality of rats and pathological symptoms were observed. Part of the animals (5 animals of each sex from each experimental group) were abandoned after the introduction to the 14-day observation and determination of these parameters.

The impact of the proposed remedies on the body weight of Wistar rats, feed and water intake, systolic blood pressure and heart rate were studied within 14 days of administration. Each experimental group consisted of 15 animals of each sex.

The results were processed statistically using t-student test at p<=0,05.

The results obtained are presented in tables 4-8.

The state and behavior of animals from different groups treated with the proposed tool, did not differ from those of the control animals. Sex differences were not observed.

Table 4

The impact of the proposed remedies on the dynamics of weight gain albino rats (M±m, g)
Time studiesThe experimental group
ControlThe proposed tool, 2.2 mg/kgThe proposed tool, 11.0 mg/kg
MFM FMF
Background184.0±3.3180.5±2.7182.5±2.9179.5±3.3181.0±2.6178.0±3.1
7 days195.0±4.5189.5±3.4193.0±4.1190.4±4.3193.2±3.5188.5±4.3
14 days206.0±5.3203.0±4.1204.5±5.2199.0±5.4205.0±5.4Has 197.5±6.1

Table 5

The impact of the proposed means for feed intake (M±m, g)
Time studiesThe experimental group
ControlThe proposed tool, 2.2 mg/kgThe proposed tool, 11.0 mg/kg
MFMFMF
Background20.0±1.020.0±2.020.0±2.021.0±1.019.5±1.520.0±2.0
14 days23.0±2.022.0±2.022.5±1.5 21.0±2.022.0±2.023.5±2.0

Table 6

The impact of the proposed funds for water consumption (M±m, ml)
Time studiesThe experimental group
ControlThe proposed tool, 2.2 mg/kgThe proposed tool, 11.0 mg/kg
MFMFMF
Background21.0±2.021.0±1.020.0±1.021.0±1.020.0±2.019.5±1.5
14 days22.5±2.023.0±1.522.0±2.022.0±2.521.5±1.522.0±1.0

As can be seen from the above tables, there were no differences in the dynamics of weight gain, feed and water intake between animals treated with the proposed tool, and control animals.

Table 7

The impact of the proposed funds for systolic blood pressure white rats (mm Hg, M±m)
Time studiesThe experimental group
ControlThe proposed tool, 2.2 mg/kgThe proposed tool, 11.0 mg/kg
MFMFMF
Background126±12139±13142±17132±13140±15138±14
14 days118±11127±9136±9128±11134±7124±10

Table 8

The impact of the proposed remedies on the variation of white rats (BPM, M±m)
Time studiesThe experimental group
ControlThe proposed tool, 2.2 mg/kgThe proposed tool, 11.0 mg/kg
MFMFMF
Background354±24372±27334±22342±30366±39388 24
14 days420±36419±31351±41384±41418±41412±32

As follows from the data presented above, significant changes from the level of blood pressure and heart rate in animals from all experimental groups were observed. Sex differences were not observed.

Table 9 presents data on the impact of the proposed funds for basic biochemical parameters of blood of white rats.

Table 9

The impact of the proposed funds for basic biochemical parameters of blood
The analyzed indicators (M±m)The drug, mg/kg
ControlThe proposed tool, 2.2 mg/kgThe proposed tool, 11.0 mg/kg
Males, 14 days
Total protein, g/l63±466±264±3
ACT, u/l0.55±0.030.56±0.030.58±0.04
ALT, u/l0.22±0.040.21±0.030.20±0.03
LDH, u/l5.06±0.335.07±0.345.02±0.30
Alkaline phosphatase, u/l0.71±0.090.69±0.100.68±0.10
Urea, mmol/l5.28±0.265.18±0.225.24±0.24
Creatinine, mmol/l0.10±0.020.11±0.030.11±0.02
Glucose, mmol/l5.2±0.35.1±0.24.9±0.3
Total lipids, g/l4.08±0.344.00±0.324.10±0.36
Cholesterol, mmol/l1.66±0.241.62±0.321.72±0.22
The total bilirubin, mmol/l12.6±0.612.4±0.412.4±0.4
Bilirubin is associated, mmol/l3.3±0.43.1±0.23.4±0.3

Na, mmol/l145±3141±2143±4
K, mmol/l5.3±0.35.4±0.25.2±0.2
The analyzed indicators (M±m)The drug, mg/kg
ControlThe proposed tool, 2.2 mg/kgOffer means the, 11.0 mg/kg
Females, 14 days
Total protein, g/l64±468±570±4
ACT, u/l0.62±0.030.64±0.050.60±0.03
ALT, u/l0.22±0.040.20±0.040.22±0.04
LDH, u/l5.02±0.304,96±0.325.04±0.31
Alkaline phosphatase, u/l0.78±0.110.82±0.150.80±0.14
Urea, mmol/l5.22±0.205.26±0.245.24±0.23
Creatinine, mmol/l0.09±0.020.11±0.020.09±0.01
Glucose, mmol/l5.1±0.25.3±0.35.2±0.2
Total lipids, g/l4.06±0.334.08±0.363.98±0.31
Cholesterol, mmol/l1.52±0.341.48±0.271.44±0.31
The total bilirubin, mmol/l11.6±0.412.1±0.411.8±0.4
Bilirubin is associated, mmol/l2.8±0.23.3±0.43.0±0.2
Na, mmol/l143±3144±3144±3
K, mmol/l5.3±0.35.5±0.35.3±0.2

As can be seen from the data presented above, the fluctuations in the values of all the studied indices are within the physiological norm.

Thus, the proposed funds within 14 days no toxic effects on protein, carbohydrate, fat and electrolyte types of metabolism of white rats.

Table 10

The impact of the proposed funds in the peripheral blood of white rats (M±m)
The analyzed indicators (M±m)The drug, mg/kg
ControlThe proposed tool, 2.2 mg/kgThe proposed tool, 11.0 mg/kg
Males, 14 days
Hemoglobin, g/l145±4144±2144±2
Erythrocytes, 1012/l6.0±0.46.5±0.36.3±0.4
ESR, mm/h4.1±0.24.0±0.34.0±0.4
Platelets, 109 /l368±21425±24382±27
Leukocytes, 109/l5.7±0.46.1±0.36.4±0.4
Stab neutrophils, %1.02±0.031.08±0.041.04±0.03
Segmentgalerie neutrophils, %16.0±6.324.3±7.921.7±5.5
Basophils, %000
Eosinophils, %2.5±0.32.0±0.32.0±0.3
Monocytes, %5.0±0.34.7±0.44.8±0.3
Lymphocytes, %74.3±1.772.8±1.369.4±1.2
The analyzed indicators (M±m)The drug, mg/kg
ControlThe proposed tool, 2.2 mg/kgThe proposed tool, 11.0 mg/kg
Females, 14 days
Hemoglobin, g/l147±3143±4145±3
Erythrocytes, 1012/l6.2±0.36.3±0.26.1±0.4
ESR, mm/h3.9±0.3 3.7±0.34.1±0.2
Platelets, 109/l412±29393±27405±19
Leukocytes, 109/l6.3±0.36.0±0.35.8±0.5
Stab neutrophils, %1.08±0.031.06±0.031.10±0.04
Segmentgalerie neutrophils, %18.4±4.320.5±5.119.8±4.4
Basophils, %000
Eosinophils, %2.2±0.22.1±0.22.3±0.2
Monocytes, %4.9±0.25.0±0.35.1±0.2
Lymphocytes, %71.6±2.168.4±1.573.2±2.2

Lymphocytes are strongly picotesla the core is sometimes found significant Ashrafinia grain. The bulk of segmented cells has a gentle, neutrophilic, not quite clear grain in smears. Kernel eosinophilic cells formed from loose chromatin substance and have an almost circular shape. Kernel eosinophils and neutrophils are formed on ringed type, so often found the annular core at Palo is davidnyc forms. Monocytes are very different from lymphocytes. The latter is equal to the value of two cells, have a great bobbygee core and wide protoplasmatic the border that is painted in blue or purple color with a delicate granulation. Blood platelets are large heaps.

Significant differences between the parameters of the control and test groups were not observed. Sex differences were not found.

Thus, the peripheral blood of rats experimental groups according to their quantitative and qualitative composition corresponded to specific physiological norm.

In table 11 presents data on the mass ratios of the organs of white rats of the experimental groups after 14 days after the start of injection. The study was conducted on 10 animals of each sex from each group.

Table 11

The impact of the proposed funds for mass ratios organs of white rats (mg/100 g)
MK (M±m)The proposed tool, mg/kg
Control2.211.0
MFMFMF
Heart4.2±0.3.9± 0.34.3±0.44.0±0.34.6±0.34.2±0.3
Light9.8±0.59.6±0.410.0±0.79.5±0.49.9±0.49.9±0.3
The thymus1.13±0.031.10±0.031.14±0.021.11±0.031.12±0.041.14±0.03
Liver53.0±5.052.0±5.054.0±3.058.0±5.057.0±5.053.0±5.0

Spleen3.5±0.33.3±0.33.4±0.43.5±0.33.3±0.43.4±0.4
Kidney8.0±0.47.8±0.58.2±0.58.1±0.48.0±0.58.0±0.3
The adrenal glands0.32±0.030.32±0.030.33±0.030.32±0.030.31±0.030.30±0.02
The brain9.6±0.49.7±0.49.8±0.68.8±0.49.5±0.59.7±0.4
The testes or ovaries14.1±0.40.44±0.0314.0±0.60.45±0.0413.2±0.50.45±0.04

The table shows that the differences between the mass ratios of the organs of rats treated with the proposed tool, and control animals was not observed. Pathological changes not.

Thus, the study showed that in the acute experiment after intragastric administration proposed funds rats-males and females significant differences in toxicometric parameters have been identified.

In the study of subacute toxicity shown that daily for 14 days intragastric administration of the proposed tools in doses exceeding the maximum daily at 10 and 50 times, does not lead to the development of pathological changes of the General condition and behavior of animals, has no toxic effects on protein, carbohydrate, fat and electrolyte types of metabolism, morphological composition of peripheral blood does not cause dystrophic and destructive, focal sclerotic changes in parenchymatous cells and stroma of the internal organs and is not accompanied locally irritant effect.

As can be seen from the obtained results of the proposed anti-inflammatory drug, done the TES in the form of solid dosage forms for oral administration, containing the active meloxicam, moving - salt of stearic acid, a binder is maltodextrin, disintegrator - in particular the sodium salt croscarmellose and filler - dextrin, has high bioavailability and improved consumer properties, as well as expands the Arsenal of anti-inflammatory action.

1. Anti-inflammatory drug, is made in the form of solid dosage forms for oral administration containing active ingredient : meloxicam, moving, a binder and a filler, wherein the binder it contains maltodextrin as a filler - dextrin, as the moving - salt of stearic acid or stearic acid, and further comprises a disintegrator, in particular the sodium salt croscarmellose, with the following content, wt.%:

Meloxicam4,0-25,0
Disintegrator - sodium salt croscarmellose0,5-7,0
Binder is maltodextrin5,0-20,0
Moving - salt of stearic acid
or stearic acid0.3 to 1.0
Filler - dextrin100

2. The tool according to claim 1, characterized in that it as a salt of stearic acid may contain magnesium or calcium salts.

3. The tool according to claim 1, characterized in that it is made in the form of tablets, or microtablets, or pellets, or granules.

4. The tool according to claim 3, characterized in that the mass of the tablet is 0.1 g and 0.2 g

5. The tool according to claim 3, characterized in that the size of microtablets is from 1.5 to 3.0 mm

6. The tool according to claim 3, characterized in that the size of the pellets or granules is 0.25 to 2.0 mm

7. The tool according to claim 3, characterized in that it can be coated on the base polymer.

8. The tool according to claim 7, characterized in that the weight of the shell relative to the mass of the nucleus is, wt.%: for tablets 5-13, for microtablets 5-13, for pellets 15-25, granules 25-40.

9. The tool according to claim 3, characterized in that a number of microtablets, or pellets, or granules may be placed in a pharmaceutically acceptable capsule for oral administration.

10. The tool according to claim 9, characterized in that the capsule is filled with microtablets, or pellets, or granules in such a quantity that the concentration of active ingredient equivalent to therapeutic dose.



 

Same patents:

FIELD: pharmaceutical industry, in particular anesthetic and vasodilating ointment.

SUBSTANCE: claimed ointment is prepared on the base of fine dispersed formulation contains apitoxin extract melittin, camphor, lavender, rosemary and eucalyptus oils and revitalin in specific component ratio. Ointment of present invention is useful in treatment of reumathysm, muscle and joint diseases, myodynia, radiculitis, ischias, neurodynia, polyneuritis, etc.

EFFECT: ointment with reduced apiotoxin toxicity, decreased side effects and improved therapeutic effect.

2 tbl

FIELD: pharmaceutical industry, in particular production of ointment having antiinflammation and antimicrobial activity.

SUBSTANCE: method for ointment production includes extraction of ground dogwood stones with chloroform during certain time followed by solvent removing and isolation of lipophilic fraction. Then dried solvent cake from dogwood stones is extracted with boiled purified water, solvent is removed and hydrophilic fraction is isolated. Further emulsifier, petrolatum and lipophilic fraction taken in specific ratio are fused at certain temperature; mixture is cooled and blended with water purified and heated up to certain temperature; obtained mixture is blended with solution comprising purified hydrophilic fraction, glycerol and water taken in specific ratio.

EFFECT: ointment of increased antiinflammation and antimicrobial activity.

2 tbl, 6 ex

FIELD: pharmaceutical industry, in particular production of ointment having antiinflammation and antimicrobial activity.

SUBSTANCE: method for ointment production includes grinding of plant raw materials namely solid coconut husk up to certain particle size; extraction with chloroform during certain time followed by solvent removing and isolation of lipophilic fraction. Further emulsifier, lipophilic fraction and coconut oil are fused under specific conditions; mixture is cooled to certain temperature and blended with celandine juice heated up to certain temperature.

EFFECT: ointment of increased antiinflammation and antimicrobial activity.

3 tbl, 15 ex

FIELD: organic chemistry, medicine, rheumatology.

SUBSTANCE: invention proposes a medicinal agent comprising derivative of aminostilbazol as an active component of the formula : or its salt wherein G represents phenyl optionally substituted with (C1-C6)-alkoxy-group; R represents (1) hydrogen atom, (2) (C1-C6)-hydroxyalkyl, or (3) the group -CORo wherein Ro represents (C1-C6)-alkyl, (C1-C6)-alkoxy-, phenoxy-group. The preferable compound is (E)-4-{2-[2-{N-acetyl-N-[(4-methoxyphenyl)sulfonyl]amino}phenyl]ethenyl}pyridine 1-oxide. The proposed agent is designated for treatment of chronic articular rheumatism.

EFFECT: realization of invention, valuable medicinal properties of agent.

7 cl, 2 tbl, 7 ex

FIELD: medicine.

SUBSTANCE: invention relates to new 5-amino-exo-3-azatricyclo[5.2.1.02,6]-decan-4-one of formula I having excellent arrhythmic, anti-inflammation, analgesic, and noothropic activity and low toxicity.

EFFECT: new pharmaceutical preparation.

3 tbl, 8 ex

FIELD: biochemistry, nucleotides, pharmacy.

SUBSTANCE: invention relates to using adenosine 5'-triphosphate-2',3'-dialdehyde for preparing analgesic medicinal agent.

EFFECT: valuable medicinal property of agent.

2 tbl, 3 dwg, 2 ex

FIELD: medicine, pharmacy.

SUBSTANCE: invention relates to inflammatory agents. Invention proposes the ointment that comprises liquid potassium humate, birch tar, sodium silicate, vaseline wherein the potassium liquid humate comprises the humic substances in the amount 4.5 g/l, not less. Invention provides enhancing storage time, stability, high effectiveness and the broad spectrum of effect.

EFFECT: valuable medicinal and pharmaceutical properties of ointment.

2 cl, 6 ex

FIELD: medicine.

SUBSTANCE: method involves applying cannabinoid receptor agonists for treating for transitory relaxation of lower esophageal sphincter and states like gastroesophageal reflux disease, regurgitation, preventing reflux or insufficient mass increase caused by the relaxation.

EFFECT: enhanced effectiveness of treatment.

18 cl, 3 tbl

FIELD: medicine, gynecology, phytotherapy, pharmaceutical industry.

SUBSTANCE: invention relates to composition used in treatment of gynecological diseases in women. The composition for treatment of gynecological diseases in women comprises a mixture of the following dry medicinal plants: pot-marigold flowers, clinging bedstraw herb, swampy marsh cinquefoil herb, walnut walls, licorice roots and fenestrate Saint-John's-wort herb taken in the definite ratio of components. Also, the composition for treatment of gynecological diseases in women comprises a mixture of 30-40% alcoholic tinctures of medicinal plants: pot-marigold flowers, clinging bedstraw herb, swampy marsh cinquefoil herb, walnut walls, licorice roots and fenestrate Saint-John's-wort herb taken in the definite ratio. Proposed compositions promote to effective treatment of gynecological diseases in women.

EFFECT: valuable medicinal properties of compositions.

4 cl, 6 ex

FIELD: biotechnology, in particular utilization of strain Lactobacillus salivarius UCC 118 for prophylaxis and/or treatment of undesired inflammation activity and cancer prophylaxis.

SUBSTANCE: human-original strain Lactobacillus salivarius UCC 118[NCIMB 40829] is isolated from dissected and washed human gastrointestinal tract. Strain application makes it possible to decelerate development of malignant diseases and to reduce undesired inflammation activity such as intestine inflammation or irritable colon.

EFFECT: strain for prophylaxis and/or treatment of undesired inflammation activity and cancer prophylaxis.

42 cl, 29 dwg, 1 tbl, 4 ex

FIELD: medicine, pharmacy.

SUBSTANCE: invention proposes a hydrophilic pharmaceutical composition with hypoglycemic effect comprising nateglinide crystals of B-type as an active component. The composition has edge angle to water surface 111 degrees or less. This edge angle is created by addition at least one hydrophilic substance to the composition chosen from groups comprising of hydrophilic polymers, surfactants, sugars and sugar-alcohols. Invention provides easy method for preparing the composition, its high solubility and rather rapid release of nateglinide.

EFFECT: improved and valuable properties of pharmaceutical composition.

13 cl, 8 dwg, 4 tbl, 6 ex

FIELD: pharmaceutical composition in form of tablet, sachet or powder for suspension.

SUBSTANCE: claimed composition contains particles of azithromicine non-dehydrated form obtained by dry granulation method and optionally one or more pharmaceutically acceptable excipient. Pharmaceutical composition preferably represents tablet containing approximately 40-85 mass % non-dehydrated azithromicine. More preferably pharmaceutical composition contains non-dehydrated azithromicine selected from F, G, J, M forms or mixtures thereof. Most preferably pharmaceutical composition contains azithromicine (A) in dose of 250 mgA, 500 mgA, 600 mgA, or 1000 mgA. Also disclosed is azithromicine particles obtained by dry granulation method that containing azithromicine form selected from F, G, J, M forms and mixtures of non-dehydrated forms, and at least one pharmaceutically acceptable excipient.

EFFECT: new azithromicine compositions.

17 cl, 7 tbl, 7 ex

FIELD: pharmaceutical and food industries.

SUBSTANCE: invention relates to preparing water-soluble or water-dispersible carbohydrate-based powders and tablets. Carbohydrate matrix is composed of at least 90% carbohydrate, e.g. starch or sugar. Closed-porosity powder or tablet is treated with gas so that gas contained in pores enhances dissolution or dispersing when in contact with water. Gas can be selected from nitrogen, carbon dioxide, air, oxygen, helium, hydrogen, argon, neon, methane, ethane, krypton, chlorine, chlorofluorocarbon, and mixture thereof. Gas is forced preferably under pressure at temperature above Tg of carbohydrate. Powder or tablet can further contain protein, hydrocolloid, or fat and forms no foam on dissolution or dispersing.

EFFECT: improved consumer's property of powders and tablets.

35 cl, 1 dwg, 2 tbl, 5 ex

FIELD: medicine, pharmaceutical technology, pharmacy.

SUBSTANCE: invention relates to producing solid combined medicinal formulations of preparations exhibiting an antihypertensive effect, increasing heart blow-out index and enhancing tolerance to physical load in patient with the congestive cardiac insufficiency. The proposed medicinal agent comprises the following components, wt.-%: perindopril erbumine, 0.6-7.0; microcrystalline cellulose, 12.0-35.0; magnesium stearate, 0.3-1.7; aerosil, 0.1-1.0; croscarmelose-sodium, 1.1-7.0, and lactose, the balance. Also, invention discloses a method for preparing the medicinal formulation. Invention reduces loss of perindopril in process for the formulation preparing, retaining the parent properties of perindopril erbumine and enhancing biological availability of agent.

EFFECT: enhanced and valuable properties of agent, improved preparing method.

3 cl, 2 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: invention relates to polyvitamin composition comprising complex of vitamins A, B1, B2, B6, B12, C, E, nicotinamide and calcium pantothenate and, optionally, folic acid, biotin, chlorocalciferol, phytomenadione and sorbitol, lactose, lubricating agent, taste and/or odor corrector as special supplements, and, optionally, microcrystalline cellulose and/or aerosil, and to a method for its preparing. The composition shows the enhanced stability.

EFFECT: improved and valuable properties of composition.

19 cl, 1 tbl, 4 ex

FIELD: medicine, ophthalmology, chemical-pharmaceutical industry, pharmacy.

SUBSTANCE: invention relates to the development of the ophthalmic composition possessing with anti-histaminic activity. Anti-histaminic ophthalmic drops comprise zinc sulfate, diphenhydramine hydrochloride, naphazoline hydrochloride, sodium citrate, citric acid, benzalkonium chloride, methylene blue, sodium chloride, hydroxypropylmethylcellulose-4000, sodium hydroxide and distilled water taken in the definite weight ratio. Drops can be used in allergic conjunctivitis, blepharitis, eyelid nettle rash and insect stings. Invention provides expanding spectrum of pharmacological effect of agent in such diseases.

EFFECT: improved and valuable medicinal properties of drops.

2 cl, 2 ex

FIELD: medicine, gastroenterology, pharmaceutical industry and technology.

SUBSTANCE: invention relates to a method for producing tablets possessing anti-ulcerous and anti-acid effect. Tablets comprise bismuth basic nitrate, magnesium basic carbonate, sodium hydrocarbonate, buckthorn bark powder, sweet flag rhizomes powder and filling agents - potato starch and calcium stearate. Method involves roasting buckthorn bark and sweet flag rhizomes under the definite conditions followed by pouring with boiling water at stirring up to preparing the homogenous suspension, mixing the suspension with other components, carrying out the wet granulation, drying the mixture, dry granulation, powdering and tableting. Method provides producing tablets showing good solubility in digestive tract and broader spectrum of effect.

EFFECT: improved and valuable medicinal and pharmaceutical properties of tablets.

1 tbl, 2 ex

FIELD: pharmaceutical technology, pharmacy.

SUBSTANCE: invention relates to producing solid combined medicinal formulations of preparations showing the hypotensive effect on both systolic and diastolic arterial blood pressure, increasing the cardiac blood ejection and enhancing the tolerance to physical loading. Proposed medicinal agent comprises the following components, wt.-%: perindopril erbumin, 0.6-6.6; indapamide, 0.1-2.1; microcrystalline cellulose, 16.0-35.0; magnesium stearate, 0.3-1.7; aerosil, 0.2-1.0; croscarmelose sodium, 1.1-7.5, and lactose, the balance. Also, invention discloses a method for preparing the medicinal formulation. Invention provides reducing mechanical losses of perindopril erbumin and indapamide in the process of the formulation preparing, retaining their properties in intact state and enhancing biological availability of active substances.

EFFECT: improved and enhanced medicinal and pharmaceutical properties of agent.

3 cl, 2 tbl, 2 ex

FIELD: chemical-pharmaceutical industry, pharmacy.

SUBSTANCE: invention relates to an agent possessing anti-coughing and expectorative effects. Agent possessing anti-coughing and expectorative effects comprises codeine, sodium hydrocarbonate, terpin hydrate, potato starch, stearic acid, nutritive gelatin and medicinal talc in the following ratio of components, g per a tablet of mass 0.6 g: codeine, 0.008; sodium hydrocarbonate, 0.3; terpin hydrate, 0.2; potato starch, 0.0617; stearic acid, 0.0053; nutritive gelatin, 0.01, and medicinal talc, 0.015. Invention provides safety in prolonged intake of the agent that shows less expressed irritant effect on stomach mucosa.

EFFECT: improved and valuable medicinal and pharmaceutical properties of agent.

5 tbl

FIELD: medicine, pharmaceutical technology, pharmacy.

SUBSTANCE: invention relates to a method for preparing methyluracil-base preparation representing stimulating agent of leucopoiesis in form of a tablet. The proposed method is carried out by mixing an active substance that is taken in the therapeutically permitted amount with accessory additives followed by granulation and tableting. Lactose and starch taken in the ratio 2:1 are used as accessory additives. After mixing all components the prepared mass is wetted firstly with 5% solution of medium-molecular polyvinylpyrrolidone followed by rewetting with 10% solution of polyvinylpyrrolidone wherein the total amount of mean-molecular polyvinylpyrrolidone is 5-5.5% of the total weight. The wet mass is granulated and dried at temperature 45-55°C and vacuum value 0.7-0.9 kgf/cm2 up to the residual moisture 3.5-4.0%. Then 8-10% of granules of their total amount are powdered with aerosil and calcium stearate taken in equal parts in the amount 0.5-0.8% of the total amount of the preparation followed by addition of other amount of granulate and tableting the prepared mixture. Invention provides simplified technology and simultaneous creature of a simple and available formulation of the medicinal agent as a tablet, enhanced strength of tablet and simultaneous rapid breaking up tablet in water, enhanced stability of tablet at storage.

EFFECT: improved preparing method, improved and valuable medicinal and pharmaceutical properties of preparation.

2 tbl, 1 ex

FIELD: medicine, narcology, biochemistry, pharmacy.

SUBSTANCE: invention proposes using the combination of dextromethorphan and the second medicine (quinidine, yohimbin, haloperdol, adjmaline, lobeline, pipamperon, fluoxetine, labetalol, chlorpromazine, domperidone, nortryptiline, quinine, oxyprenolol, propranolol, timolol, methaprolol, diphenhydramine, papaverine, mexiletine or their salts or isomers) for removing addiction to opiates, opioids or synthetic narcotics with exception cocaine and barbiturates (help in refusal in their using) or in case of chronic using antidepressant and corresponding treatment methods. The proposed combination of drugs reduces pain and relieves the withdrawal syndrome on the background of reducing morphine dose (antidepressant) up to the complete removing their intake.

EFFECT: enhanced effectiveness and valuable medicinal properties of medicine combinations.

54 cl, 2 ex

Up!